In diabetes mellitus some aspects of cell-mediated immunity are defective. The overall long-term objective of this proposal is to elucidate the mechanism(s) for the defects in cell-mediated immunity observed in diabetes mellitus. The approach used is infection of control and diabetic animals with the facultative intracellular parasite, Listeria monocytogenes. Preliminary results suggest that Listeria monocytogenes proliferates to a greater extent in diabetic animals, and dermal hypersensitivity is delayed in diabetes. These studies suggest that the defect(s) in cell-mediated immunity in diabetic animals may be at the level of the effector T-lymphocyte, the macrophage or in lymphokine production. The reversibility of these defects by insulin administration will be studied.